The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair.

Defective DNA damage response is a threat to genome stability and a proven cause of tumorigenesis. C21ORF2 (chromosome 21 open reading frame 2) is a novel gene on chromosome 21, and the C21ORF2 protein is found to interact with NEK1. Earlier studies showed that C21ORF2 might be associated with some human genetic diseases including Down syndrome. However, the cellular functions of C21ORF2 remain unknown. In the present study, we reported that C21ORF2 affected cell proliferation after DNA damage induced by ionizing radiation, and DNA repair was less efficient in C21ORF2-depleted cells compared with control cells. However, C21ORF2-knockdown cells did not show defects in the activation of the G2-phase DNA damage checkpoint. Furthermore, homologous recombination, but not non-homologous end joining repair, was found to be impaired after C21ORF2 attenuation, which could be rescued by the overexpression of NEK1, indicating that C21ORF2 functions in the same pathway as NEK1 in DNA damage repair.

[1]  L. Zou,et al.  Nek1 kinase associates with ATR–ATRIP and primes ATR for efficient DNA damage signaling , 2013, Proceedings of the National Academy of Sciences.

[2]  V. Stambolic,et al.  Nek family of kinases in cell cycle, checkpoint control and cancer , 2011, Cell Division.

[3]  D. Chan,et al.  Analysis of the Human Endogenous Coregulator Complexome , 2011, Cell.

[4]  S. Elledge,et al.  The DNA damage response: making it safe to play with knives. , 2010, Molecular cell.

[5]  J. Marine,et al.  Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death , 2010, Nature Cell Biology.

[6]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[7]  G. Peng,et al.  BRIT1/MCPH1 Links Chromatin Remodeling to DNA Damage Response , 2009, Nature Cell Biology.

[8]  D. Riley,et al.  Never-in-mitosis related Kinase 1 functions in DNA damage response and checkpoint control , 2008, Cell cycle.

[9]  F. D. D. Fagagna.  Living on a break: cellular senescence as a DNA-damage response , 2008, Nature Reviews Cancer.

[10]  L. Quarmby,et al.  The NIMA-family kinase, Nek1 affects the stability of centrosomes and ciliogenesis , 2008, BMC Cell Biology.

[11]  Y. Altschuler,et al.  The mammalian Nek1 kinase is involved in primary cilium formation , 2008, FEBS letters.

[12]  J. Hoeijmakers.  Genome maintenance mechanisms for preventing cancer , 2001, Nature.

[13]  J. Nickoloff,et al.  Regulation of DNA double-strand break repair pathway choice , 2008, Cell Research.

[14]  J. Błasiak,et al.  DNA damage and repair in children with Down's syndrome. , 2008, Mutation research.

[15]  J. Bergelson,et al.  Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain. , 2003, Journal of neural transmission. Supplementum.